Testosterone replacement maintains smooth muscle content in the corpus cavernosum of orchiectomized rats
Graziele Halmenschlagera, Ernani Luis Rhodenb, Gabriela Almeida Mottac, Lucas Sagrillo Fagundesd, Jorge Luiz Medeiros Jre,f, Rosalva Meurerc, Cláudia Ramos Rhodenc
a Centro Universitário Ritter dos Reis (UniRitter) and Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA)-PPG Ciências da Saúde, Porto Alegre, RS, Brazil;
b Department of Urology at Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Urologist at Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA) and Hospital Moinhos de Vento de Porto Alegre (HMV), Porto Alegre, RS, Brazil;
c Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA)-PPG Ciências da Saúde-Porto Alegre, RS, Brazil;
d INRS Institut Armand Frappier (Universit. du Québec) and BioMed Research Center Laval, Quebec, Canada;
e Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil;
f Laboratory of Multidisciplinary of Sciences, Biomedical Center, Medical School of Valença, Valença/Rio de Janeiro, Brazil
AbstractObjective: To evaluate the effects of testosterone (T) on the maintenance of corpus cavernosum (CC) structure and apoptosis. Methods: Animals were divided into three groups:sham operation group (n=8) underwent sham operation; Orchiectomized (Orchiec)+oily vehicle group (n=8) underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection (i.m.) 30 days after orchiectomy; and Orchiec+T group (n=8) underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m. 30 days after the surgery. Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine. Blood samples and penile tissue were collected on euthanasia.Azan's trichrome staining was used to evaluate smooth muscle,Weigert's Fucsin-Resorcin staining was used to evaluate elastic fibers and Picrosirius red staining was used to evaluate collagen.Apoptosis was evaluated using TUNEL technique. Results: T levels decreased in Orchiec + oily vehicle when compared to sham operation and Orchiec + T groups (p < 0.001).T deprivation reduced trabecular smooth muscle content and penile diameter and T replacement maintained both parameters (p = 0.005 and p = 0.001,respectively).No difference was observed in the content of sinusoidal space (p = 0.207),elastic fibers (p = 0.849),collagen (p = 0.216) and in apoptosis (p= 0.095). Conclusion: Normal testosterone levels maintain CC smooth muscle content and do not influence elastic fibers,collagen content and apoptotic index.Further studies should be performed in order to investigate the mechanisms by which androgen mediates its effects on CC structure.
Fund:We thank Urogenital Research Unit staff, UERJ, for technical support and UFCSPA, CNPq (MCT/CNPq 15/2007), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES and FAPERGS (11/1003-5-02/2011) for financial support.
Graziele Halmenschlager,Ernani Luis Rhoden,Gabriela Almeida Motta, et al. Testosterone replacement maintains smooth muscle content in the corpus cavernosum of orchiectomized rats[J]. Asian Journal of Urology,
2017, 4(4): 223-229.
Traish AM. Androgens play a pivotal role in maintaining penile tissue architecture and erection:a review. J Androl 2009;30:363-9.
[2]
Traish AM, Goldstein I, Kim NN. Testosterone and erectile function:from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur Urol 2007;52:54-70.
[3]
Gurbuz N, Mammadov E, Usta FM. Hypogonadism and erectile dysfunction:an overview. Asian J Androl 2008;10:36-43.
[4]
Rhoden EL, Telöken C, Sogari PR, Souto CA. The relationship of serum testosterone to erectile function in normal aging men. J Urol 2002;167:1745-8.
[5]
Traish AM, Park K, Dhir V, Kim NN, Moreland RB, Goldstein I. Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 1999;140:1861-8.
[6]
Traish AM, Munarriz R, O'Connel L, Choi S, Kim SW, Huang YH, et al. Effects of medical or surgical castration on erectile function in an animal model. J Androl 2003;24:381-7.
[7]
Miranda AF, Gallo CB, de Souza DB, Costa WS, Sampaio FJ. Effects of castration and late hormonal replacement in the structure of rat corpora cavernosa. J Androl 2012;33:1224-32.
[8]
Zhang XH, Hu LQ, Zheng XM, Li SW. Apoptosis in rat erectile tissue induced by castration. Asian J Androl 1999;1:181-5.
[9]
Callies F, Kollenkirchen U, von zurMuhlen C, Tomaszewski M, Beer S, Allolio B. Testosterone undecanoate:a useful tool for testosterone administration in rats. Exp Clin Endocrinol Diabetes 2003;111:203-8.
[10]
Abidu-Figueiredo M, Ribeiro IC, Chagas MA, Cardoso LE, Costa WS, Sampaio FJ. The penis in diabetes:structural analysis of connective tissue and smooth muscle alterations in a rabbit model. BJU Int 2011;108:400-4.
[11]
Montes GS, Junqueira LC. The use of the picrosiriuspolarization method for the study of the biopathology of collagen. Mem Inst Oswaldo Cruz 1991;86(Suppl. 3):1-11.
[12]
Felix-Patrício B, De Souza DB, Gregório BM, Costa WS, Sampaio FJ. How to quantify penile corpus cavernosum structures with histomorphometry:comparison of two methods. Biomed Res Int 2015;2015:832156. http://dx.doi.org/10.1155/2015/832156.
[13]
User HM, Hairston JH, Zelner DJ, McKenna KE, McVary KT. Penileweightandcellsubtypespecificchanges in a post-radicalprostatectomymodeloferectiledysfunction. J Urol 2003;169:1175-9.
[14]
Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev 1995;75:191-236.
[15]
Nehra A, Goldstein I, Pabby A, Nugent M, Huang YH, de lasMorenas A, et al. Mechanisms of venous leakage:a prospective clinicopathological correlation of corporeal function and structure. J Urol 1996;156:1320-9.
[16]
Shen ZJ, Zhou XL, Lu YL, Chen ZD. Effect of androgen deprivation on penile ultrastructure. Asian J Androl 2003;5:33-6.
[17]
Yamamoto H, Sasaki S, Tatsura H, Umemoto Y, Kubota H, Kamiya H, et al. Penile apoptosis in association with p53 under lack of testosterone. Urol Res 2004;32:9-13.
[18]
Kiess W, Gallaher B. Hormonal control of programmed cell death/apoptosis. Eur J Endocrinol 1998;138. 482 e 91.
[19]
Nakazawa R, Tanaka M, Takahashi T, Kobayashi S, Iwamoto T. Effects of castration and testosterone administration on angiotensin Ⅱ receptor mRNA expression and apoptosis-related proteins in rat urinary bladder. Endocr J 2007;54:211-9.
[20]
Lorenzetti F, Pintarelli VL, Seraphim DC, Dambros M. Low testosterone levels induce apoptosis via active 3-caspase dependent signaling in the bladder wall of male rats. Aging Male 2012;15:216-9.
[21]
Shabsigh R. The effects of testosterone on the cavernous tissue and erectile function. World J Urol 1997;15:21-6.
[22]
Pinheiro AC, Costa WS, Cardoso LE, Sampaio FJ. Organization and relative content of smooth muscle cells, collagen and elastic fibers in the corpus cavernosum of rat penis. J Urol 2000;164:1802-6.
[23]
Costa WS, Carrerete FB, Horta WG, Sampaio FJ. Comparative analysis of the penis corpora cavernosa in controls and patients with erectile dysfunction. BJU Int 2006;97:567-9.
[24]
Inoue T, Miki Y, Abe K, Hatori M, Hosaka M, Kariya Y, et al. Sex steroid synthesis in human skin in situ:the roles of aromatase and steroidogenic acute regulatory protein in the homeostasis of human skin. Mol Cell Endocrinol 2012;362:19-28.
